Back to resultsA Study to Assess the Safety and Pharmacokinetics of an Inhibitor of Poly ADP-Ribose Polymerase-1 (PARP)
Primary Purpose
Ovarian Neoplasms, BRCA1 Protein, BRCA2 Protein
Status
Completed
Phase
Phase 1
Locations
International
Study Type
Interventional
Intervention
KU-0059436 (AZD2281)(PARP inhibitor)
Sponsored by
About this trial
This is an interventional treatment trial for Ovarian Neoplasms focused on measuring advanced ovarian cancer, BRCA 1 protein, BRCA 2 protein, Poly(ADP ribose)polymerases
Eligibility Criteria
Inclusion Criteria:
- Confirmed malignant advanced solid tumour refractory to standard therapy or for which no suitable effective standard therapy exists.
Exclusion Criteria:
- Anti-cancer therapy including chemotherapy, radiotherapy, endocrine therapy, immunotherapy or use of other investigational agents within the 4 weeks prior to trial entry (or a longer period depending on the defined characteristics of the agents used).
Sites / Locations
- Research Site
- Research Site
- Research Site
- Research Site
- Research Site
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
KU-0059436
Arm Description
KU-0059436 administered orally twice daily
Outcomes
Primary Outcome Measures
To determine the safety, tolerability, dose-limiting toxicity (DLT), and (MTD) of KU-0059436
Secondary Outcome Measures
Objective tumour response
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT00516373
Brief Title
A Study to Assess the Safety and Pharmacokinetics of an Inhibitor of Poly ADP-Ribose Polymerase-1 (PARP)
Official Title
A Phase I, Pharmacokinetic and Biological Evaluation of a Small Molecule Inhibitor of Poly ADP-Ribose Polymerase-1 (PARP-1), KU-0059436, in Patients With Advanced Tumours.
Study Type
Interventional
2. Study Status
Record Verification Date
June 2023
Overall Recruitment Status
Completed
Study Start Date
July 11, 2005 (Actual)
Primary Completion Date
December 17, 2008 (Actual)
Study Completion Date
April 26, 2023 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
AstraZeneca
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
To determine the safety, tolerability, dose-limiting toxicity (DLT), pharmacokinetic-pharmacodynamic profile, and maximum tolerated dose (MTD) of KU-0059436 when administered orally to patients with advanced solid tumours. To further evaluate the safety and efficacy of KU-0059436 in an expanded cohort of BCRA-enriched population, primarily ovarian cancer patients
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Ovarian Neoplasms, BRCA1 Protein, BRCA2 Protein
Keywords
advanced ovarian cancer, BRCA 1 protein, BRCA 2 protein, Poly(ADP ribose)polymerases
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
98 (Actual)
8. Arms, Groups, and Interventions
Arm Title
KU-0059436
Arm Type
Experimental
Arm Description
KU-0059436 administered orally twice daily
Intervention Type
Drug
Intervention Name(s)
KU-0059436 (AZD2281)(PARP inhibitor)
Other Intervention Name(s)
Olaparib
Intervention Description
oral
Primary Outcome Measure Information:
Title
To determine the safety, tolerability, dose-limiting toxicity (DLT), and (MTD) of KU-0059436
Time Frame
assessed at each visit
Secondary Outcome Measure Information:
Title
Objective tumour response
Time Frame
assessed every 8 weeks
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
130 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Confirmed malignant advanced solid tumour refractory to standard therapy or for which no suitable effective standard therapy exists.
Exclusion Criteria:
Anti-cancer therapy including chemotherapy, radiotherapy, endocrine therapy, immunotherapy or use of other investigational agents within the 4 weeks prior to trial entry (or a longer period depending on the defined characteristics of the agents used).
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Jane Robertson, BSc, MBCHB, MD
Organizational Affiliation
AstraZeneca
Official's Role
Study Director
First Name & Middle Initial & Last Name & Degree
Dr. Johann De Bono, PhD MRCP FRCR
Organizational Affiliation
Royal Marsden Hospital Trust, London, UK
Official's Role
Principal Investigator
Facility Information:
Facility Name
Research Site
City
Brussels
ZIP/Postal Code
1090
Country
Belgium
Facility Name
Research Site
City
Amsterdam
ZIP/Postal Code
1066 CX
Country
Netherlands
Facility Name
Research Site
City
Szczecin
ZIP/Postal Code
70-115
Country
Poland
Facility Name
Research Site
City
Edinburgh
ZIP/Postal Code
EH4 2XR
Country
United Kingdom
Facility Name
Research Site
City
London
ZIP/Postal Code
SM2 5NG
Country
United Kingdom
12. IPD Sharing Statement
Plan to Share IPD
Yes
IPD Sharing Plan Description
Qualified researchers can request access to anonymized individual patient-level data from AstraZeneca group of companies sponsored clinical trials via the request portal. All request will be evaluated as per the AZ disclosure commitment: https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure
IPD Sharing Time Frame
AstraZeneca will meet or exceed data availability as per the commitments made to the EFPIA Pharma Data Sharing Principles. For details of our timelines, please rerefer to our disclosure commitment at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure
IPD Sharing Access Criteria
When a request has been approved AstraZeneca will provide access to the de-identified individual patient-level data in an approved sponsored tool . Signed Data Sharing Agreement (non-negotiable contract for data accessors) must be in place before accessing requested information. Additionally, all users will need to accept the terms and conditions of the SAS MSE to gain access. For additional details, please review the Disclosure Statements at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure
IPD Sharing URL
https://astrazenecagroup-dt.pharmacm.com/DT/Home
Citations:
PubMed Identifier
26961146
Citation
Matulonis UA, Penson RT, Domchek SM, Kaufman B, Shapira-Frommer R, Audeh MW, Kaye S, Molife LR, Gelmon KA, Robertson JD, Mann H, Ho TW, Coleman RL. Olaparib monotherapy in patients with advanced relapsed ovarian cancer and a germline BRCA1/2 mutation: a multistudy analysis of response rates and safety. Ann Oncol. 2016 Jun;27(6):1013-1019. doi: 10.1093/annonc/mdw133. Epub 2016 Mar 8.
Results Reference
derived
PubMed Identifier
23922302
Citation
Ang JE, Gourley C, Powell CB, High H, Shapira-Frommer R, Castonguay V, De Greve J, Atkinson T, Yap TA, Sandhu S, Banerjee S, Chen LM, Friedlander ML, Kaufman B, Oza AM, Matulonis U, Barber LJ, Kozarewa I, Fenwick K, Assiotis I, Campbell J, Chen L, de Bono JS, Gore ME, Lord CJ, Ashworth A, Kaye SB. Efficacy of chemotherapy in BRCA1/2 mutation carrier ovarian cancer in the setting of PARP inhibitor resistance: a multi-institutional study. Clin Cancer Res. 2013 Oct 1;19(19):5485-93. doi: 10.1158/1078-0432.CCR-13-1262. Epub 2013 Aug 6.
Results Reference
derived
PubMed Identifier
19553641
Citation
Fong PC, Boss DS, Yap TA, Tutt A, Wu P, Mergui-Roelvink M, Mortimer P, Swaisland H, Lau A, O'Connor MJ, Ashworth A, Carmichael J, Kaye SB, Schellens JH, de Bono JS. Inhibition of poly(ADP-ribose) polymerase in tumors from BRCA mutation carriers. N Engl J Med. 2009 Jul 9;361(2):123-34. doi: 10.1056/NEJMoa0900212. Epub 2009 Jun 24.
Results Reference
derived
Links:
URL
http://filehosting.pharmacm.com/DownloadService.ashx?client=CTR_MED_7111&studyid=2678&filename=CSR_Synopsis_D0810C00002(KU36-92).pdf
Description
CSR_Synopsis_D0810C00002(KU36-92).pdf
Learn more about this trial
A Study to Assess the Safety and Pharmacokinetics of an Inhibitor of Poly ADP-Ribose Polymerase-1 (PARP)
We'll reach out to this number within 24 hrs